Angiotensin i-converting enzyme (ACE) inhibitory peptides

Abstract

The present disclosure provides fish-derived peptides with ACE inhibitory activity, and methods of producing peptide isolates comprising the fish-derived peptides. The present disclosure also provides pharmaceutical products, dietary supplements, and functional foods including the peptide isolates, and method of lowering blood pressure of a subject by administering to the subject one or more of the fish-derived peptides.

The invention claimed is: 
     
       1. A method of producing a peptide isolate, comprising the steps of:
 mixing fish meat with water to produce an aqueous mixture; 
 adjusting the pH of the aqueous mixture to a basic pH; 
 hydrolyzing the fish meat by adding an alkaline protease to the aqueous mixture and incubating the aqueous mixture under conditions sufficient to produce a hydrolysate and; 
 extracting the peptide isolate from the hydrolysate, wherein the peptide isolate consists of the amino acid sequence of VIYSR (SEQ ID NO: 6). 
 
     
     
       2. The method of  claim 1 , wherein the aqueous mixture comprises a ratio of meat to water of about 1:2 to about 1:3. 
     
     
       3. The method of  claim 1 , wherein the aqueous mixture comprises a protein concentration in a range of about 5% (w/v) to about 15% (w/v) (g protein/ml water). 
     
     
       4. The method of  claim 1 , wherein the basic pH is in the range of above 7 to about 11. 
     
     
       5. The method of  claim 1 , wherein the alkaline protease comprises a serine protease. 
     
     
       6. The method of  claim 1 , wherein the conditions sufficient to produce a hydrolysate comprise incubating for a time period in a range of about 2 hours to about 5 hours. 
     
     
       7. The method of  claim 1 , wherein the conditions sufficient to produce a hydrolysate comprise incubating at a temperature in the range of about 40° C. to about 70° C. 
     
     
       8. The method of  claim 1 , wherein the method further includes a step of removing cellular debris from the hydrolysate following the hydrolyzing step. 
     
     
       9. The method of  claim 8 , wherein the removing cellular debris comprises centrifuging and filtering the hydrolysate to obtain a supernatant. 
     
     
       10. The method of  claim 1 , wherein the hydrolyzing step further includes terminating a hydrolysis reaction by heating the hydrolysate to a temperature in a range of about 80° C. to about 100° C. following the incubating the aqueous mixture under conditions sufficient to produce the hydrolysate. 
     
     
       11. The method of  claim 10 , wherein the terminating the hydrolysis reaction includes incubating the hydrolysate at the temperature in the range of about 80° C. to about 100° C. for a time period in a range of about 10 minutes to about 20 minutes. 
     
     
       12. The method of  claim 1 , wherein the method further comprises a step of subjecting the hydrolysate to chromatography, and collecting one or more chromatography fractions including the peptide consisting of the amino acid sequence according to VIYSR (SEQ ID NO: 6). 
     
     
       13. The method of  claim 1 , wherein the fish meat comprises raw fish dark meat, ground fish meat, tuna meat, skipjack tuna meat, or any combination thereof. 
     
     
       14. A method of treating hypertension in a subject in need thereof comprising administering to the subject a peptide, wherein the peptide consists of the amino acid sequence according to VIYSR (SEQ ID NO: 6).